Anemia (AmE) or
anæmia/anaemia (BrE),
from the Greek ()
(an-haîma) meaning "without blood," is defined as a qualitative or
quantitative deficiency of hemoglobin, a molecule inside
red
blood cells (RBCs). As hemoglobin carries oxygen from the lungs to the
tissues,
anemia leads to hypoxia
(lack of oxygen) in organs. Since all human cells depend on
oxygen for survival,
varying degrees of anemia can have a wide range of clinical
consequences.

The three main classes of anemia include
excessive blood loss (acutely such as a hemorrhage or chronically
through low-volume loss), excessive blood cell destruction
(hemolysis) or
deficient red blood cell production (ineffective hematopoiesis).

Anemia is the most common disorder of the blood.
There are several kinds of anemia, produced by a variety of
underlying causes. Anemia can be classified in a variety of ways,
based on the morphology of RBCs, underlying etiologic mechanisms,
and discernible clinical spectra, to mention a few.

There are two major approaches of classifying
anemias, the "kinetic" approach which involves evaluating
production, destruction and loss, and the "morphologic" approach
which groups anemia by red blood cell size. The morphologic
approach uses a quickly available and cheap lab test as its
starting point (the MCV).
On the other hand, focusing early on the question of production may
allow the clinician more rapidly to expose cases where multiple
causes of anemia coexist.

Signs and symptoms

Anemia goes undetected in many people,
and symptoms can be small and vague. Most commonly, people with
anemia report a feeling of weakness or fatigue in general or during
exercise, general malaise and sometimes poor
concentration. People with more severe anemia often report dyspnea (shortness of breath) on
exertion. Very severe anemia prompts the body to compensate by
increasing cardiac
output, leading to palpitations and sweatiness,
and to heart
failure.

Pallor (pale skin,
mucosal linings and nail beds) is
often a useful diagnostic sign in moderate or severe anemia, but it
is not always apparent. Other useful signs are cheilosis and koilonychia.

Pica, the
consumption of non-food such as dirt, paper, wax, grass and hair,
may be a symptom of iron deficiency, although it occurs often in
those who have normal levels of hemoglobin.

Chronic anemia may result in behavioral
disturbances in children as a direct result of impaired
neurological development in infants, and reduced scholastic
performance in children of school age.

Diagnosis

Generally, clinicians request complete
blood counts in the first batch of blood tests in the diagnosis
of an anemia. Apart from reporting the number of red blood
cells and the hemoglobin level, the
automatic
counters also measure the size of the red blood cells by
flow
cytometry, which is an important tool in distinguishing between
the causes of anemia. Examination of a stained blood smear
using a microscope
can also be helpful, and is sometimes a necessity in regions of the
world where automated analysis is less accessible.

In modern counters, four parameters (RBC count,
hemoglobin concentration, MCV
and
RDW) are measured, allowing others (hematocrit,
MCH and
MCHC) to be calculated, and compared to values adjusted for age
and sex. Some counters estimate hematocrit from direct
measurements. For adult men, a hemoglobin level less than 13.0 g/dl
(grams per deciliter) is diagnostic of anemia, and for adult women,
the diagnostic threshold is below 12.0 g/dl.

Reticulocyte counts, and the "kinetic" approach
to anemia, have become more common than in the past in the large
medical centers of the United States and some other wealthy
nations, in part because some automatic counters now have the
capacity to include reticulocyte counts. A reticulocyte count is a
quantitative measure of the bone marrow's
production of new red blood cells. The
reticulocyte production index is a calculation of the ratio
between the level of anemia and the extent to which the
reticulocyte count has risen in response. If the degree of anemia
is significant, even a "normal" reticulocyte count actually may
reflect an inadequate response.

If an automated count is not available, a
reticulocyte count can be done manually following special staining
of the blood film. In manual examination, activity of the bone
marrow can also be gauged qualitatively by subtle changes in the
numbers and the morphology of young RBCs by examination under a
microscope. Newly formed RBCs are usually slightly larger than
older RBCs and show polychromasia. Even where the source of blood
loss is obvious, evaluation of erythropoiesis can help
assess whether the bone marrow will be able to compensate for the
loss, and at what rate.

When the diagnosis remains difficult, a bone
marrow examination allows direct examination of the precursors
to red cells.

Classification

Production vs. destruction or loss

The "kinetic" approach
to anemia yields what many argue is the most clinically relevant
classification of anemia. This classification depends on evaluation
of several hematological parameters, particularly the blood
reticulocyte
(precursor of mature RBCs) count. This then yields the
classification of defects by decreased RBC production versus
increased RBC destruction and/or loss. Clinical signs of loss or
destruction include abnormal peripheral
blood smear with signs of hemolysis; elevated LDH
suggesting cell destruction; or clinical signs of bleeding, such as
guiaic-positive stool, radiographic findings, or frank
bleeding.

Here is a simplified schematic of this
approach:

* For instance, sickle cell anemia with
superimposed iron deficiency; chronic gastric bleeding with B12 and
folate deficiency; and other instances of anemia with more than one
cause. ** Confirm by repeating reticulocyte count: ongoing
combination of low reticulocyte production index, normal MCV and
hemolysis or loss may be seen in bone marrow failure or anemia of
chronic disease, with superimposed or related hemolysis or blood
loss.

Red blood cell size

In the morphological approach, anemia
is classified by the size of red blood cells; this is either done
automatically or on microscopic examination of a peripheral blood
smear. The size is reflected in the mean
corpuscular volume (MCV). If the cells are smaller than normal
(under 80 fl), the
anemia is said to be microcytic; if they are normal size (80-100
fl), normocytic; and if they are larger than normal (over 100 fl),
the anemia is classified as macrocytic. This scheme quickly exposes
some of the most common causes of anemia; for instance, a
microcytic anemia is often the result of iron
deficiency. In clinical workup, the MCV will be one of the
first pieces of information available; so even among clinicians who
consider the "kinetic" approach more useful philosophically,
morphology will remain an important element of classification and
diagnosis.

Here is a schematic representation of how to
consider anemia with MCV as the starting point: Other
characteristics visible on the peripheral smear may provide
valuable clues about a more specific diagnosis; for example,
abnormal white
blood cells may point to a cause in the bone
marrow.

Microcytic anemia

Microcytic anemia is primarily a result
of hemoglobin synthesis failure/insufficiency, which could be
caused by several etiologies:

Iron deficiency anemia is the most common type of
anemia overall and it has many causes. RBCs often appear
hypochromic (paler than usual) and microcytic (smaller than usual)
when viewed with a microscope.

Iron deficiency anemia is caused by insufficient dietary intake
or absorption of iron to
replace losses from menstruation or losses due to diseases. Iron is
an essential part of hemoglobin, and low iron levels result in
decreased incorporation of hemoglobin into red blood cells. In the
United States, 20% of all women of childbearing age have iron
deficiency anemia, compared with only 2% of adult men. The
principal cause of iron deficiency anemia in premenopausal women is
blood lost during menses. Studies have shown
that iron deficiency without anemia causes poor school performance
and lower IQ in
teenage girls. Iron deficiency is the most prevalent deficiency
state on a worldwide basis. Iron deficiency is sometimes the cause
of abnormal fissuring of the angular (corner) sections of the lips
(angular
stomatitis).

Macrocytic anemia

Megaloblastic
anemia, the most common cause of macrocytic anemia, is due to a
deficiency of either vitamin B12,
folic
acid (or both). Deficiency in folate and/or vitamin B12 can be
due either to inadequate intake or insufficient absorption.
Folate deficiency normally does not produce neurological symptoms,
while B12 deficiency does.

Pernicious
anemia is an autoimmune condition thought
to be due to a directed attack against intrinsic
factor produced by the parietal
cells of the stomach. Intrinsic factor is required to absorb
vitamin B12 from food. Therefore, the destruction of intrinsic
factor, leads to poor absorption of vitamin B12.

Macrocytic anemia can also be caused by removal of the
functional portion of the stomach, such as during gastric
bypass surgery, leading to reduced vit B12/folate absorption.
Therefore one must always be aware of anemia following this
procedure.

Macrocytic anemia can be further divided into
"megaloblastic anemia" or "non-megaloblastic macrocytic anemia".
The cause of megaloblastic anemia is primarily a failure of DNA
synthesis with preserved RNA synthesis, which result in restricted
cell division of the progenitor cells. The megaloblastic anemias
often present with neutrophil hypersegmentation (6-10 lobes). The
non-megaloblastic macrocytic anemias have different etiologies
(i.e. there is unimpaired DNA globin synthesis,) which occur, for
example in alcoholism.

The treatment for vitamin B12-deficient anemia
was first devised by William
Murphy who bled dogs to make them anemic and then fed them
various substances to see what (if anything) would make them
healthy again. He discovered that ingesting large amounts of liver
seemed to cure the disease. George
Minot and George
Whipple then set about to chemically isolate the curative
substance and ultimately were able to isolate the vitamin B12
from the liver. All three shared the 1934
Nobel Prize in Medicine.

Dimorphic anemia

When two causes of anemia act
simultaneously, e.g., macrocytic hypochromic, due to hookworm infestation leading to
deficiency of both iron and
vitamin
B12 or folic acid or
following a blood
transfusion more than one abnormality of red cell indices may
be seen. Evidence for multiple causes appears with an elevated RBC
distribution width (RDW), which suggests a wider-than-normal range
of red cell sizes.

Heinz body anemia

Heinz bodies
are an abnormality that form on the cells in this condition. This
form of anemia may be brought on by taking certain medications; it
is also triggered in cats by
eating onions or acetaminophen (Tylenol).
It can be triggered in dogs
by ingesting onions or zinc, and in horses by ingesting
dry red
maple leaves.

Specific anemias

Anemia
of prematurity occurs in premature infants at 2 to 6 weeks of
age and results from diminished erythropoietin response to
declining hematocrit levels

Hemolytic
anemia causes a separate constellation of symptoms (also
featuring jaundice and
elevated LDH
levels) with numerous potential causes. It can be autoimmune, immune, hereditary
or mechanical (e.g. heart
surgery). It can result (because of cell fragmentation) in a
microcytic anemia, a normochromic anemia, or (because of premature
release of immature red blood cells from the bone marrow), a
macrocytic anemia.

Hereditary
spherocytosis is a hereditary defect that results in defects in
the RBC cell membrane, causing the erythrocytes to be sequestered
and destroyed by the spleen. This leads to a decrease in the number
of circulating RBCs and, hence, anemia.

Myelophthisic
anemia or Myelophthisis
is a severe type of anemia resulting from the replacement of bone
marrow by other materials, such as malignant tumors or
granulomas.

Possible complications

Anemia diminishes the capability of
individuals who are affected to perform physical activities. This
is a result of one's muscles being forced to depend on anaerobic
metabolism. The lack of iron associated with anemia can cause
many complications, including hypoxemia,
brittle
or rigid fingernails, cold intolerance, and possible behavioral
disturbances in children. Hypoxemia resulting from anemia can
worsen the cardio-pulmonary status of patients with pre-existing
chronic pulmonary disease. Cold intolerance occurs in one in five
patients with iron deficiency anemia, and becomes visible through
numbness and tingling.

Anemia during pregnancy

Anemia affects 20% of all females
of childbearing age in the United States. Because of the subtlety
of the symptoms, women are often unaware that they have this
disorder, as they attribute the symptoms to the stresses of their
daily lives. Possible problems for the fetus include increased risk
of growth retardation, prematurity, intrauterine death, rupture
of the amnion and
infection.

During pregnancy, women should be especially
aware of the symptoms of anemia, as an adult female loses an
average of two milligrams of iron daily. Therefore, she must intake
a similar quantity of iron in order to make up for this loss.
Additionally, a woman loses approximately 500 milligrams of iron
with each pregnancy, compared to a loss of 4-100 milligrams of iron
with each period.
Possible consequences for the mother include cardiovascular
symptoms, reduced physical and mental performance, reduced immune
function, tiredness, reduced peripartal blood reserves and
increased need for blood transfusion in the postpartum
period.

Treatments for anemia

There are many different treatments
for anemia and the treatment depends on severity and the
cause.

Iron deficiency from nutritional causes is rare
in non-menstruating adults (men and post-menopausal women). The
diagnosis of iron deficiency mandates a search for potential
sources of loss such as gastrointestinal bleeding from ulcers or
colon cancer. Mild to moderate iron deficiency anemia is treated by
iron supplementation with ferrous
sulfate or ferrous gluconate. Vitamin C may
aid in the body's ability to absorb iron.

In severe cases of anemia, or with ongoing blood
loss, a blood transfusion may be necessary.

Blood transfusions for anemia

Doctors attempt to avoid
blood
transfusion in general, since multiple lines of evidence point
to increased adverse patient clinical outcomes with more intensive
transfusion strategies. The physiological principle that reduction
of oxygen delivery associated with anemia leads to adverse clinical
outcomes is balanced by the finding that transfusion does not
necessarily mitigate these adverse clinical outcomes.

In severe, acute bleeding, transfusions of
donated blood are often lifesaving. Improvements in battlefield casualty
survival is attributable, at least in part, to the recent
improvements in blood banking and transfusion techniques.

Transfusion of the stable but anemic hospitalized
patient has been the subject of numerous clinical
trials, and transfusion is emerging as a deleterious
intervention.

Four randomized controlled clinical trials have
been conducted to evaluate aggressive versus conservative
transfusion strategies in critically ill patients. All four of
these studies failed to find a benefit with more aggressive
transfusion strategies.

In addition, at least two retrospective studies
have shown increases in adverse clinical outcomes with more
aggressive transfusion strategies.